It is the purpose of this study to investigate at a mechanical, hemodynamic and subcellular level the defect in myocardial function as a result of surgically induced glogal ischemia and reperfusion. Since mechanical measures of myocardial function necessitates reperfusion, ischemic injury will be documented by identifying specific subcellular defects (Sarcoplasmic Reticulum Calcium flux and ATPase activity, Myofibrillar ATPase activity and Calcium binding and Sarcolemma Na plus K ion ATPase and Adenylate Cyclase. Based on this information, the first objective of this study will be to design specific protection against ischemic injury. Three possible protective mechanisms will be addressed: 1) Lysosomal stabilization; 2) Sarcolemmal stabilization; and 3) Proton Sequestration. The second objective of this study, based on the preceeding information, will become the definition and characterization of reperfusion injury. This will be accomplished by designing a sophisticated model of reperfusion with internal controls. Reperfusion injury will be characterized as either a primary form of tissue injury or an extension of ischemic injury defined as uneven reperfusion creating localized areas of myocardial oxygen supply to demand imbalance. Mechanical function (dP/dt-max, plus dP/dt, -dP/dt, and isovolumetric LV pressure before and after catecholamine stimulation) will be correlated with coronary hemodynamics (total and regional myocardial flow and coronary vascular resistance) and subcellular function. Any imbalance in reperfusion flow will be documented on both a physiological and anatomic bases. Based on this information, specific protection will be designed to minimize or eliminate reperfusion injury and will include direct coronary vasodilators, modification of the perfusate, platelet inhibition and the new concept of sequential reperfusion. The third objective of this study will then evaluate these findings on the intact myocardium on a hemodynamic, mechanical and subcellular basis and extend the concept of afterload reduction to the post-operative heart.